Glucagon‐like peptide‐1 receptor agonists for antipsychotic‐associated cardio‐metabolic risk factors: A systematic review and individual participant data meta‐analysis

Patients with schizophrenia have higher cardio-metabolic risk, partially from antipsychotic-induced weight-gain. Glucagon-like-peptide-1 receptor-agonists (GLP-1RAs) may reduce antipsychotic-associated weight-gain, however, safety and efficacy in schizophrenia has not been systematically reviewed. We systematically searched PubMed/EMBASE/PsycINFO/Cochrane, using the search terms "(antipsychotic and GLP-1RA)". Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. Primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic parameters and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic parameter, ADRs, and GLP-1RA-agent. Three studies (exenatide once-weekly=2; liraglutide once-daily=1) provided participant-level data (n=164, age=40.0±11.1years, weight=105.8±20.8kg). After 16.2±4.0 weeks of treatment, weight loss was 3.71 kg (95% CI=2.44-4.99 kg) greater for GLP-1RA vs. control (p GLP-1RAs are effective and tolerable for antipsychotic-associated weight-gain, particularly clozapine-/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs. This article is protected by copyright. All rights reserved.